Matrix Metalloproteinase (MMP) and A Disintegrin And Metalloproteinase (ADAM) are a family of structurally-related zinc-containing enzymes. MMPs are secreted as inactive proenzymes, which become active enzymes following proteolytic cleavage of the peptide amino-terminal domain or conformational modification.
MMPs and ADAMs are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling. Defects in the regulation of these enzymes can result in pathological destruction of the tissue. A wide range of diseases or disorders may result from the loss of regulation control of matrix metalloproteinases, such as multiple sclerosis, restenosis, aortic aneurism, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chromic ulcers or wounds, cancer metastasis, tumor angiogenesis, arthritis, psoriasis and autoimmune and inflammatory diseases arising from tissue invasion by leukocytes.
Previous studies have suggested that inhibition of MMPs and ADAMs may be applicable in the treatment of diseases.
WO 01/26661 [1] concerns alpha-oxophosphonates or alpha-thioxophosphonates as effective compounds in inhibiting zinc containing proteinases, particularly matrix metalloproteinases, to control the invasiveness of cancer cells.
WO 04/089962 [2] concerns a specific group of compounds having carbamoyl- or thiocarbamoylphosphonate functionalities and are considered to be improved MMP-2 inhibitors.
Rossello A. et al., [3] report on new N-arylsulfonyl-N-alkoxyamino acetohydroxamic acid as selective inhibitors of MMP-2.
Wada C. K. et al., [4] report on a group of compounds having a phenoxyphenyl functionality which are selective for inhibition of MMP-2 and MMP-9 over MMP-1.
Shyh-Ming Yang et al., [5] report on a series of β-N-biaryl ether sulfonamide hydroxamates as of MMP-2 and MMP-9 inhibitors.
Reiter L. A. et al., [6] report on a series of selective pyrimidinetrione-based inhibitors of MMP-13.
Hoffman A. et al., [7] report on carbamoylphosphonate derivatives for use as MMP inhibitors.